. Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments. Science. 2019 May 17;364(6441) PubMed.


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  1. Axonal protein synthesis is a mechanism to alter the local proteome in a spatially and temporally restricted manner. Many studies have demonstrated its importance in virtually every aspect of axonal biology, e.g., developmental growth, regeneration, synapse formation. In contrast, the question of whether protein synthesis occurs at the mature presynapse has remained controversial.

    Hafner et al. are now providing direct evidence from rodent brain and cultured neurons that protein synthesis happens routinely at both sides of mature CNS synapses. While the function of presynaptic protein synthesis remains unknown, the finding that protein synthesis is differentially regulated at excitatory and inhibitory presynapses, and in response to distinct forms of plasticity, suggests a direct role in synapse function. 

    Exposure to soluble oligomeric Aβ1-42 changes the axonally localized transcriptome and increases axonal protein synthesis. In the context of AD, it will be especially interesting to determine how Aβ1-42-induced changes in axonal mRNA localization and protein synthesis affect the presynaptic proteome, and whether synaptic dysfunction in AD is at least in part mediated by changes to presynaptic protein synthesis.

    View all comments by Ulrich Hengst
  2. Dr. Hafner is correct in stating that analyzing the nuclear transcriptome "will miss information about the subcellular distribution of transcripts and local regulation of translation." I spearheaded a study of the synaptic transcriptome in MCI/incipient AD brains, published in 2009. Although the study focused on dendritic mRNA transcripts, we also detected axonal transcripts with altered expression.


    . Transcriptome analysis of synaptoneurosomes identifies neuroplasticity genes overexpressed in incipient Alzheimer's disease. PLoS One. 2009;4(3):e4936. PubMed.

    View all comments by Celia Williams
  3. I’d like to thank Celia Williams for bringing her paper to my attention. It is very interesting. I am not surprised she identified both dendritic and axonal genes. Synaptoneurosomes, as she beautifully shows in EM, have the particularity to be composed of both a presynaptic terminal and a postsynaptic spine, both with closed membranes.

    In fact, I have compared the excitatory presynaptic transcriptome and the list of dysregulated transcripts in Alzheimer from Dr. Williams’ study. Among the 13 presynaptically localized transcripts that are dysregulated during AD, there are: KIF1A, a kinesin implicated in anterograde axonal transport; SNRK, a kinase identified as a potential mediator of neuronal apoptosis; and GRK2 (ADRBK1), a kinase already identified as an early marker of AD.

    View all comments by Anne-Sophie Hafner

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  1. Plasticity Hums With Protein Synthesis on Both Sides of Synapse